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Docetaxel Tied to Less Taxane Neuropathy in Black Breast Cancer Patients

— Dose-limiting toxicity has been linked with worse outcomes specifically in this population

MedpageToday

CHICAGO -- Germline variations did not predict the risk of taxane-induced peripheral neuropathy (TIPN) in a phase II trial involving Black women with early-stage breast cancer, but the researchers found that docetaxel was associated with a significantly lower incidence of moderate to severe TIPN than paclitaxel for these patients.

The primary purpose of the study was to validate whether certain genetic variants confer a high risk of TIPN in Black women -- FCAMR GG (homozygous wild-type) or SBF2 mutations -- given that this population is more likely to be affected by the dose-limiting toxicity and potentially suffer worse survival as a result.

While three-fourths of the women with the high-risk genotype had numerically greater rates of TIPN versus those with the low-risk genotype -- variant allele in FCAMR (AG or AA) and SBF2 wild-type -- the differences were not statistically significant in the total population or in either of the taxane arms:

  • Total population: 38% vs 26% (P=0.15)
  • Docetaxel: 28% vs 19% (P=0.47)
  • Paclitaxel: 47% vs 35% (P=0.27)

"It's likely that those variants do contribute to neuropathy, but it's very multifactorial," said Tarah Ballinger, MD, of the Bren Simon Comprehensive Cancer Center and Indiana University School of Medicine in Indianapolis, who presented the findings during a press briefing at the American Society of Clinical Oncology (ASCO) meeting. "We need to look at more inherited and non-inherited factors in this population."

However, the findings revealed that moderate to severe TIPN (meaning grade ≥2) occurred at a significantly lower rate in the every-3-week docetaxel arm at 1 year compared with the once-weekly paclitaxel arm, both when the toxicity was reported by the physicians (25% vs 44%, P=0.004) or by the patients (24% vs 40%).

Furthermore, dose reductions for TIPN at this point occurred in only 8.5% of the docetaxel arm versus 28.1% of the paclitaxel arm (P<0.001), dose reductions for any reason were also lower with docetaxel (24.6% vs 38.8%, P=0.019), and there were no survival differences at 2 years.

"This trial does have important implications for Black women with early-stage breast cancer," said Ballinger, who added that the results suggest that every-3-week docetaxel "may be the better taxane option specifically for Black women, for whom neuropathy is more common and severe, and impacts their disease outcomes."

Findings from the prospective study were published simultaneously in the .

ASCO's Chief Medical Officer Julie Gralow, MD, who moderated the press briefing, noted that the once-weekly paclitaxel regimen used in the study is the most common dosing strategy in early-stage breast cancer.

"It's very clear that for peripheral neuropathy, docetaxel versus weekly paclitaxel has less peripheral neuropathy," she said. "There are other toxicities with these drugs, although this is one that has some very serious long-term effects, so we do rate the peripheral neuropathy benefit very highly."

It's well-established that Black women have worse outcomes when it comes to breast cancer; not only are they more likely to die of their disease but they also have higher rates of dose-limiting toxicities, explained Ballinger.

And prior studies have shown that dose reductions of taxane therapy are associated with lower cure rates specifically in Black patients, a relationship not seen in white patients, she said. But often the studies included low numbers of Black women that lacked sufficient power for proper statistical analysis.

"So here we have a disparity in a toxicity that's ultimately impacting equitable outcomes in breast cancer," said Ballinger.

Gralow noted that the trial can serve as a blueprint for powering studies that examine other toxicities that disproportionately affect underrepresented populations. "I think that involving the community, as you did, was an important part of why you were able to accrue to this study," she told Ballinger.

Gralow was referring to the fact that Ballinger's team sought out the help of Black patient advocates to help with enrollment, along with a social media campaign that featured Black women with breast cancer. Many of the patients enrolled from sites in the National Cancer Institute's Community Oncology Research Program.

Ballinger presented findings from , a phase II trial that exclusively enrolled Black women with stage I-III breast cancer (N=240) already planning to receive (neo)adjuvant taxane therapy for their cancer. Patients were excluded if they had pre-existing neuropathy or had received prior taxane therapy. Based on disease characteristics and physician's choice, the women received either weekly paclitaxel (n=120) or docetaxel every 3 weeks (n=120) at the standard dosing and durations.

Median age of the population was 54 years, about three-fourths had an Eastern Cooperative Oncology Group performance status of 0, and more than 80% had stage I-II disease. A little less than half had estrogen receptor-positive/HER2-negative disease, 37% were triple-negative, and 14% were HER2-positive. Overall, 75.7% were classified as having the high-risk genotype for TIPN, while 24.3% had the low-risk genotype.

The primary objective was to prospectively validate the identified germline predictors of TIPN, with secondary objectives including comparisons of grade ≥2 TIPN and dose reductions between arms at 12 months. Other objectives included patient-reported outcomes, survival, and other toxicities.

At data cutoff, there were no differences in relapse-free survival (RFS) or overall survival (OS) between the two taxane drugs, with 2-year RFS rates of 93% with docetaxel and 88% with paclitaxel (P=0.26) and 2-year OS rates of 95% and 96%, respectively (P=0.78).

Significant differences in other grade ≥2 adverse events included more mucositis and bone pain in the docetaxel group and more leukopenia, lymphocytopenia, and alopecia in the paclitaxel group.

While past studies in breast cancer patients of all races and ethnicities have found a higher risk of TIPN with older age, increased body mass index (BMI), and diabetes, the current study only found an association with increased BMI.

  • author['full_name']

    Ian Ingram is Managing Editor at 51˶ and helps cover oncology for the site.

Disclosures

The National Cancer Institute funded the study.

Ballinger reported honoraria from TerSera.

Gralow had no disclosures.

Primary Source

American Society of Clinical Oncology

Ballinger TJ "ECOG-ACRIN EAZ171: Prospective validation trial of germline variants and taxane type in association with taxane-induced peripheral neuropathy (TIPN) in Black women with early-stage breast cancer" ASCO 2024; LBA503.

Secondary Source

Journal of Clinical Oncology

Schneider BP, et al "ECOG-ACRIN EAZ171: Prospective validation trial of germline predictors of taxane-induced peripheral neuropathy in black women with early-stage breast cancer" J Clin Oncol 2024; DOI: 10.1200/JCO.24.00526.